POS1320 SAFETY AND EFFICACY OF RITUXIMAB IN PATIENTS WITH JUVENILE SYSTEMIC LUPUS ERYTHEMATOSUS: THE PRELIMINARY DATA OF RETROSPECTIVE COHORT STUDY
Authors: E. Kalashnikova, R. Raupov, N. Lybimova, E. Kuchinskaya, O. Kalashnikova, V. Chasnyk, T. Kornishina, L. Snegireva, E. Gaidar, V. Masalova, E. Isupova, M. Kaneva, M. Dubko, T. Likhacheva, L. Sorokina, M. Kostik
Journal: Annals of the Rheumatic Diseases (2022)

Background juvenile systemic lupus erythematosus (jSLE) is the most frequent pediatric connective tissue disease with multiorgan involvement and different outcomes and prognosis. Corticosteroids remain the base treatment option and steroid-sparing treatment is strongly required to avoid steroid toxicity. Rituximab (RTX) is one of biologics, which efficacy was proved in case reports and case series of SLE, but no data from big randomized trials, confirming the efficacy have existed. Objectives to evaluate safety and efficiency of RTX in jSLE. Methods in the retrospective observation study the information of 48 jSLE patients (12 boys, 36 girls) who received at least one RTX dose before 18 years, included. Diagnosis was made using SLICC criteria. The main indications for RTX were high disease activity with lupus nephritis (LN), CNS and hematology disturbances (hemolytic anemia, thrombocytopenia) and avoiding steroid toxicity. RTX was prescribed in dosage 375 mg/m 2 every week (2-4 infusions) with repeated courses every 6-12 months according disease activity, the degree of B-cell depletion and hypoIgG-emia. The dynamics of clinical, laboratory data, activity of the disease by SLEDAI, GCS doses were assessed in the onset and during RTX trial. Results The main patient’s characteristics were: onset age 13.0 (11.5; 15.0) years, inclusion age 18.0 (16.0; 20.0) years, LN 25 (52%)/III+IV class 9/11 (82%), CNS involvement 26 (54%). Pre-RTX non-biologic conventional treatment includes: cyclophosphamide 24 (50%), MMF 14 (29%), azathyoprine 7 (15%), methotrexate 6 (13%), cyclosporine A 2 (4%). Observation period ranged from 6 months to 6 years with median time 0.75 (0.2; 2.75) years. Initial pre-RTX treatment (GCS, hydroxychloroquine, non-biologic DMARDS) partially reduced SLE activity (SLEDAI, ANA titer, anti-dsDNA level), and median GCS dose by 25% from the initial dose, without changes in proteinuria, hematuria, C3, C4, WBC, hemoglobin, PLT and ESR levels. Administration of the RTX realized in prominent reducing of SLEDAI, anti-dsDNA level, proteinuria, hematuria, C4, ESR, number of patients with anemia, thrombocytopenia, and median GCS dose by 90% from the initial. The hemoglobin level and WBC have increased. 19 patients received IVIG for treatment of MAS (n=3), infection (n=5) and as replacement treatment in cases where IgG&lt;4.5 g/l (n=11). 3 deaths were observed due to catastrophic SLE with MAS, accompanied severe infection (invasive aspergillosis, n=2). 6 patients realized SAE: pneumonia (n=3), transient agranulocytosis (n=1) after 3 rd RTX infusion and meningitis, caused by Lysteria monocytogenis, after 1 st RTX infusion (further RTX treatment continued without adverse events), patella osteomyelitis (n=1). 10 patients received antibiotics for respiratory infections. On pre-RTX 13 had antibiotics (p=1.0). Table 1. Dynamics of SLE features pre-RTX and during RTX trial Parameter SLE onset RTX (baseline) p Last visit p* SLEDAI 16 (11.0; 23.5) 13.5 (6.5; 21.5) 0.0002 4 (0; 8.0) 0.00002 Patients with elevated anti-dsDNA n, (%) 33 (69) 20 (42) 0.008 11 (23) 0.034 Anti-dsDNA, U/ml (n.v.&lt;25) 112 (1; 200) 24.7 (1; 130) 0.059 0 (0; 27) 0.008 Proteinuria, g/l 2.6 (0.8; 4.4) 3.8 (0.3; 7.5) 0.687 0 (0; 0.2) 0.004 Hematuria, # cells 40 (8; 86) 50 (6; 120) 0.191 0 (0; 1) 0.0016 C4, g/l 0.12 (0.1; 0.24) 0.12 (0.06; 0.19) 0.398 0.15 (0.11; 0.21) 0.016 Patients with leucopenia, n(%) 12 (25) 10 (21) 0.629 5 (10) 0.00001 Patients with anemia n (%) 19 (40) 16 (33) 0.09 7 (15) 0.0015 Hemoglobin, g/l 113 (95;131) 115 (91; 132) 0.830 128 (107; 134) 0.063 Patients with thrombocytopenia n (%) 17 (35) 9 (19) 0.005 2 (4) 0.00001 ESR, mm/h 17 (8; 31) 15 (7; 22) 0.134 7 (2; 20) 0.054 Patients with GCS therapy n, (%) 45 (94) 45 (94) 1.0 40 (83) 0.00001 GCS, mg/kg 1.0 (0.6; 1.0) 0.75 (0.2; 1.0) 0.035 0.1 (0.08; 0.28) 0.000001 *compare to RTX baseline Conclusion RTX showed effectiveness in the cases, where previous non-biologic treatment was insufficiently effective. Randomized controlled trials are required to evaluate the efficacy and safety of RTX. Acknowledgements This research was funded by the Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2020-901) Disclosure of Interests None declared